ANK2

This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

Ankyrin 2

Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity).

Atrial cardiac muscle cell action potential Source: BHF-UCL
Atrial cardiac muscle cell to AV node cell communication Source: BHF-UCL
Atrial septum development Source: BHF-UCL
Cellular calcium ion homeostasis Source: BHF-UCL
Cellular protein localization Source: BHF-UCL
Endocytosis Source: UniProtKB-KW
Endoplasmic reticulum to Golgi vesicle-mediated transport Source: Reactome
Membrane depolarization during SA node cell action potential Source: BHF-UCL
Positive regulation of calcium ion transmembrane transporter activity Source: BHF-UCL
Positive regulation of calcium ion transport Source: BHF-UCL
Positive regulation of cation channel activity Source: BHF-UCL
Positive regulation of gene expression Source: BHF-UCL
Positive regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
Positive regulation of potassium ion transport Source: BHF-UCL
Protein localization to cell surface Source: BHF-UCL
Protein localization to endoplasmic reticulum Source: BHF-UCL
Protein localization to M-band Source: BHF-UCL
Protein localization to organelle Source: BHF-UCL
Protein localization to plasma membrane Source: BHF-UCL
Protein localization to T-tubule Source: BHF-UCL
Protein stabilization Source: BHF-UCL
Protein transport Source: UniProtKB-KW
Regulation of atrial cardiac muscle cell action potential Source: BHF-UCL
Regulation of calcium ion transmembrane transporter activity Source: BHF-UCL
Regulation of calcium ion transport Source: BHF-UCL
Regulation of cardiac muscle cell contraction Source: BHF-UCL
Regulation of cardiac muscle contraction Source: BHF-UCL
Regulation of cardiac muscle contraction by calcium ion signaling Source: BHF-UCL
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
Regulation of heart rate Source: BHF-UCL
Regulation of heart rate by cardiac conduction Source: BHF-UCL
Regulation of protein stability Source: BHF-UCL
Regulation of release of sequestered calcium ion into cytosol Source: BHF-UCL
Regulation of SA node cell action potential Source: BHF-UCL
Regulation of ventricular cardiac muscle cell membrane repolarization Source: BHF-UCL
SA node cell action potential Source: BHF-UCL
SA node cell to atrial cardiac muscle cell communication Source: BHF-UCL
Sarcoplasmic reticulum calcium ion transport Source: BHF-UCL
T-tubule organization Source: BHF-UCL
Ventricular cardiac muscle cell action potential Source: BHF-UCL

Cytoskeleton; Lysosome; Early endosome; Recycling endosome; Apical cell membrane; Cell membrane; Postsynaptic cell membrane; T-tubule; Mitochondrion; Membrane; M line; Z line. Expressed at the apical membrane of airway lung epithelial cells (By similarity). Localized to the plasma membrane of the inner segments of photoreceptors in retina. Colocalizes with SPTBN1 in a distinct intracellular compartment of neonatal cardiomyocytes (PubMed:19007774). In skeletal muscle, localizes to neuromuscular junctions (By similarity). Localizes with puncta at mitochondria ends. Colocalizes and cotransports on motile vesicles with RABGAP1L (By similarity).

Long QT syndrome 4 (LQT4): A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 4 shows many atypical features compared to classical long QT syndromes, including pronounced sinus bradycardia, polyphasic T waves and atrial fibrillation. Cardiac repolarization defects may be not as severe as in classical LQT syndromes and prolonged QT interval on EKG is not a consistent feature.

Phosphorylated at multiple sites by different protein kinases and each phosphorylation event regulates the protein's structure and function.